Intramyocardial pressure becomes high in systole and decreases in diastole. Therefore, the transmural pressure of the intramyocardial vessels is pulsatile, resulting in the cyclic distension of these vessels. However, the effect of pulsatility on the behavior of the coronary resistance vessels has not been evaluated. To assess the influence of pulsatile pressure on the behavior of the coronary arterioles, we measured the luminal cross-sectional area (CSA) of coronary arterioles under cyclically changing transmural pressure. Isolated porcine coronary arterioles (internal diameter, 100 to 150 microns) were cannulated with two micropipettes and pressurized with square waves (1 Hz) through both pipettes so as not to induce flow-dependent vasodilation. During the presence (active, induced by acetylcholine; n = 7) or absence (passive, abolished by bradykinin; n = 7) of vascular tone, the CSA was measured under the following conditions: (1) The amplitude of the pressure pulse was changed at a fixed mean pressure. (2) The mean pressure was changed at a fixed pressure pulse. With increasing pulse pressure, the mean CSA at steady state increased under active conditions, whereas it decreased under passive conditions (P < .0001). This vasodilatory effect of pulse pressure remained present after endothelial denudation (P < .0001; n = 6 vessels with basal tone, n = 9 vessels with U46619-induced tone). The mean steady state CSA under passive conditions increased with the mean pressure (P < .05), whereas under active conditions it remained constant in the range of mean pressures between 50 and 100 mm Hg, reflecting myogenic responsiveness. These results indicate that an increase in amplitude of the pressure pulse dilates coronary arterioles. The vasodilating effect of the pulsation may compensate partly for the extra compressing effect of cardiac contraction on the intramyocardial vessels.